@article {13013, title = {Human xeno-autoantibodies against a non-human sialic acid serve as novel serum biomarkers and immunotherapeutics in cancer}, journal = {Cancer Res}, volume = {71}, number = {9}, year = {2011}, note = {

Cancer Res.\ 2011 May 1;71(9):3352-63. doi: 10.1158/0008-5472.CAN-10-4102. Epub 2011 Apr 19.\ 

}, month = {May 1}, pages = {3352-63}, type = {Research Support, N.I.H., Extramural}, edition = {2011/04/21}, abstract = {

Human carcinomas can metabolically incorporate and present the dietary non-human sialic acid Neu5Gc, which differs from the human sialic acid N-acetylneuraminic acid (Neu5Ac) by 1 oxygen atom. Tumor-associated Neu5Gc can interact with low levels of circulating anti-Neu5Gc antibodies, thereby facilitating tumor progression via chronic inflammation in a human-like Neu5Gc-deficient mouse model. Here we show that human anti-Neu5Gc antibodies can be affinity-purified in substantial amounts from clinically approved intravenous IgG (IVIG) and used at higher concentrations to suppress growth of the same Neu5Gc-expressing tumors. Hypothesizing that this polyclonal spectrum of human anti-Neu5Gc antibodies also includes potential cancer biomarkers, we then characterize them in cancer and noncancer patients{\textquoteright} sera, using a novel sialoglycan microarray presenting multiple Neu5Gc-glycans and control Neu5Ac-glycans. Antibodies against Neu5Gcalpha2-6GalNAcalpha1-O-Ser/Thr (GcSTn) were found to be more prominent in patients with carcinomas than with other diseases. This unusual epitope arises from dietary Neu5Gc incorporation into the carcinoma marker Sialyl-Tn, and is the first example of such a novel mechanism for biomarker generation. Finally, human serum or purified antibodies rich in anti-GcSTn-reactivity kill GcSTn-expressing human tumors via complement-dependent cytotoxicity or antibody-dependent cellular cytotoxicity. Such xeno-autoantibodies and xeno-autoantigens have potential for novel diagnostics, prognostics, and therapeutics in human carcinomas.

}, keywords = {Adenocarcinoma/blood/immunology/therapy, Animals, Autoantibodies/*blood/immunology/*pharmacology, Breast Neoplasms/blood/immunology/therapy, Colonic Neoplasms/blood/immunology/therapy, Humans, Immunization, Immunoglobulin G/immunology/is, Passive/*methods}, isbn = {1538-7445 (Electronic)00}, url = {http://www.ncbi.nlm.nih.gov/pubmed/21505105}, author = {Padler-Karavani, V. and Hurtado-Ziola, N. and Pu, M. and Yu, H. and Huang, S. and Muthana, S. and Chokhawala, H. A. and Cao, H. and Secrest, P. and Friedmann-Morvinski, D. and Singer, O. and Ghaderi, D. and Verma, I. M. and Liu, Y. T. and Messer, K. and Chen, X. and Ajit Varki and Schwab, R.} }